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Human chorionic gonadotropin
Human chorionic gonadotropin (hCG) is a peptide hormone produced in pregnancy, that is made by the embryo soon after conception and later by the syncytiotrophoblast (part of the placenta). Its role is to prevent the disintegration of the corpus luteum of the ovary and thereby maintain progesterone production that is critical for a pregnancy in humans. hCG may have additional functions, for instance it is thought that it affects the immune tolerance of the pregnancy. Early pregnancy testing generally is based on the detection or measurement of hCG. Structure hCG is an oligosaccharide glycoprotein composed of 244 amino acids with a molecular mass of 36.7 kDa. Its total dimensions are 75x35x30 angstroms. The α (alpha) subunit is 92 amino acids long and has dimensions 60x25x15 angstroms. It is heterodimeric, with an α (alpha) subunit identical to that of luteinizing hormone (LH), follicle-stimulating hormone (FSH), and thyroid-stimulating hormone (TSH) and β (beta) subunit that is unique to hCG. βhCG is encoded by six highly homologous genes which are arranged in tandem and inverted pairs on chromosome 19q13.3 - CGB(''1'',''2'',''3'',''5'',''7'',''8''). The two subunits create a small hydrophobic core surrounded by a high surface area to volume ratio 2.8 times that of a sphere. The vast majority of the outer amino acids are hydrophilic. Function hCG interacts with the LHCG receptor and promotes the maintenance of the corpus luteum during the beginning of pregnancy causing it to secrete the hormone progesterone. Progesterone enriches the uterus with a thick lining of blood vessels and capillaries so that it can sustain the growing fetus. Due to its highly negative charge hCG may repel the immune cells of the mother, protecting the fetus during the first trimester. It has also been suggested that hCG levels are linked to the severity of morning sickness in pregnant women. Because of its similarity to LH, hCG can also be used clinically to induce ovulation in the ovaries as well as testosterone production in the testes. As the most abundant biological source is women who are presently pregnant, some organizations collect urine from gravidae to extract hCG for use in fertility treatment. Pregnancy testing Pregnancy tests measure the levels of hCG in the blood or urine to indicate the presence or absence of an implanted embryo. In particular, most pregnancy tests employ an antibody that is specific to the β-subunit of hCG (βhCG). This is important so that tests do not make false positives by confusing hCG with LH and FSH. (The latter two are always present at varying levels in the body, while hCG levels are negligible except during pregnancy.) The urine test is a chromatographic immunoassay. Published detection thresholds range from 20 to 100 mIU/ml (milli International Units per milli-liter), depending on the brand of test. The urine should be the first urine of the morning when hCG levels are highest. If the specific gravity of the urine is above 1.015, the urine should be diluted. The serum test, using 2-4 mL of venous blood, is a radioimmunoassay (RIA) that can detect βhCG levels as low as 5 mIU/ml and allows quantitation of the βhCG concentration. The ability to quantitate the βhCG level is useful in the evaluation of ectopic pregnancy and in monitoring germ cell and trophoblastic tumors. Hydatiform moles ("molar pregnancy") may produce high levels of βhCG, despite the absence of an embryo. This can lead to false positive readings of pregnancy tests. Tumor marker βhCG is also secreted by some cancers including teratomas, choriocarcinomas and islet cell tumors. When a patient is suspected of harboring a teratoma (often found in the testes and ovaries but also in the brain as a dysgerminoma), a physician may consider measuring βhCG. Elevated levels cannot prove the presence of a tumor, and low levels do not rule it out (an exception is in males who do not naturally produce βhCG). Nevertheless, elevated βhCG levels fall after successful treatment (e.g. surgical intervention or chemotherapy), and a recurrence can often be detected by the finding of rising levels. Use as medication hCG is extensively used as a parenteral medication in fertility therapy in lieu of luteinizing hormone. In the presence of one or more mature ovarian follicles, ovulation can be triggered by the administration of hCG. As ovulation will happen about 40-45 hours after the injection of hCG, procedures can be scheduled to take advantage of this time sequence. Thus, patients who undergo IVF, typically receive hCG to trigger the ovulation process, but have their eggs retrieved at about 36 hours after injection, a few hours before the eggs actually would be released from the ovary. As hCG supports the corpus luteum, administration of hCG is used in certain circumstances to enhance the production of progesterone. In the male, hCG injections are used to stimulate the leydig cells to synthesize testosterone. The intratesticular testosterone is necessary for spermatogenesis from the sertoli cells. Typical indications for hCG in men include hypogonadism and fertility treatment. hCG sold under brand names including Pregnyl®, Follutein®, Profasi®, and Novarel® use chorionic gonadotropins derived form the urine of pregnant women, while Ovidrel® is a product of recombinant technology. Novarel® and hCG from APP are typically considered generics in the United States. Recreational use with steroids In the world of performance enhancing drugs, hCG is increasingly used in combination with various Anabolic Androgenic Steroid (AAS) cycles. When AAS are put into a male body, the body's natural negative feedback loops cause the body to shut down its own production of testosterone via shutdown of the HPTA (hypothalamic-pituitary-testicular axis). High levels of AASs that mimic the body's natural testosterone trigger the hypothalamus to shut down its production of gonadotropin-releasing hormone (GnRH) from the hypothalamus. Without GnRH the pituitary gland stops releasing luteinizing hormone (LH). LH normally travels from the pituitary via the blood stream to the testes where it triggers the production and release of testosterone. Without LH, the testes shut down their production of testosterone, causing testicular atrophy ("shrinking testicles"). In males, hCG mimics LH and helps restore / maintain testosterone production in the testes. As such, hCG is commonly used during and after steroid cycles to maintain and restore testicular size as well as endogenous testosterone production. However, if hGC is used for too long and in too high a dose, the resulting rise in natural testosterone will eventually inhibit its own production via negative feedback on the hypothalamus and pituitary. References 1. Acevedo, H.F. Human chorionic gonadotropin (hCG), the hormone of life and death: a review. Journal of Experimental Therapeutics and Oncology 2 ,133 (2002) 2. Wasley, G. Pregnancy testing. What will it be? Nursing Times 30-32 (June 1985) 3. Morton, H. , Hegh, V. , Clunie, G.J.A. Immunosuppression detected in pregnant mice by rosette inhibition test. Nature 249, 459–460 (1974) 4. Wu, H. , Lustbader, J.W. , Liu, Y. , Canfield, R.E. , Hendrickson, W.A. Structure of human chroionic gonadotropin at 2.6 A resolution from MAD analysis of the selenomethionyl protein. Structure 2, 6, 545-558 (1994) 5. Cheng, S.-J. , Zheng, Z.-Q. Early Pregnancy Factor in Cervical Mucus of Pregnant Women. American Journal Of Reproductive Immunology 51, 102-105 (2004) 6. Leidinger, B. , Bielack, S. , Koehler, G. , Vieth, V. , Winkelmann, W. , Gosheger, G. High level of beta-hCG simulating pregnancy in recurrent osteosarcoma: case report and review of literature. Journal of Cancer Research & Clinical Oncology 130, 6, 357-61 (2004) 7. Knight, A.K. , Bingemann, T. , Cole, L. , Cunningham-Rundles, C. Frequent false positive beta human chorionic gonadotropin tests in immunoglobulin A deficiency. Clinical & Experimental Immunology 141, 333 (2005) 8. Wilcox, A.J. , Baird, D.D. , Dunson, D. , McChesney, R. , Weinberg, C.R. Natural limits of pregnancy testing in relation to the expected menstrual period. JAMA 286, 1759–1761 (2001) 9. Nethercliffe, J. , Trewick, A. , Samuell, C. , Leaver, R. , Woodhouse, C.R.J. False-positive pregnancy tests in patients with enterocystoplasties. BJU International. 87, 780. (2001) 10.Cole, L.A. , Khanlian, S.A. Easy fix for clinical laboratories for the false-positive defect with the Abbott AxSym total β-hCG test. USA hCG Reference Service. (2004) 11.Mahantesh, A.K. Urine pregnancy test and intrauterine inseminations. The Lancet. 363, 362 (2004) Category:Glycoproteins Category:Peptide hormones Category:Gonadotropic hormones Category:Placental hormones Category:Chemical pathology de:Humanes Choriongonadotropin fr:Gonadotrophine chorionique lt:Chorioninis gonadotropinas nl:HCG-hormoon ja:ヒト絨毛性ゴナドトロピン pl:Gonadotropina kosmówkowa ru:Хорионический гонадотропин